This proposal describes a pilot study addressing the question as to whether long term administration of psychomimetic drugs may influence neuronal plasticity. Neuroleptics and antidepressants are given to mental patients for extended periods of time; however, it is not known whether these drugs facilitate or depress lesion-induced axon sprouting, an event characteristic of neuroplasticity. This information could have significant clinical implicaions since sprouting may underlie the restitution of function lost after neurosurgery or traumatic brain injury. Tricyclic antidepressants appear to act by altering monoaminergic transmission. We will examine, therefore, noradrenergic sprouting in partially deafferented limbic regions of adult rat brain after long-term administration of imipramine (10 mg/Kg, once daily). This drug will be administered for either 3 weeks prior to lesions, or both prior to and for 27 days post-operative, i.e. one day prior to sacrificing the animals. Noradrenergic sprouting will be identified in the partially denervated habenula or hippocampal formation, by measuring norepiniphrine levels and by studying fluorescence intensity of catecholaminergic innervation. The experimental groups will be compared with the appropriate sham-treated controls. The data from this work may yield insights into the mode of imipramine action and might lay the groundwork for the development of new therapy for the treatment of mentally afflicted patients after neurosurgery or traumatic brain injury. Long-term objective are to study the influence of other antidepressants, both tricyclic and monoamine oxidase inhibitors, on the sprouting capacity of other neurons, e.g. serotoninergic, using the same model systems.